Lifestyle Interventions for Hypertension and Dyslipidemia Among Women of Reproductive Age

Introduction Hypertension and dyslipidemia often precede cardiovascular disease. Lifestyle modifications help prevent these conditions, and referrals for women may be possible during reproductive health care visits. However, screening recommendations vary, which may affect screening rates. The objectives of this systematic review were to 1) assess the available literature on the effectiveness of lifestyle interventions, 2) review hypertension and dyslipidemia screening recommendations for consistency, and 3) report prevalence data for hypertension and dyslipidemia screening among women of reproductive age. Methods We conducted a systematic literature search (January 1990-November 2010) for 1) randomized controlled trials on the impact of lifestyle interventions on cardiovascular disease risk factors in women of reproductive age, 2) evidence-based guidelines on hypertension and dyslipidemia screening, and 3) population-based prevalence studies on hypertension or dyslipidemia screening or both. Results Twenty-one of 555 retrieved studies (4%) met our inclusion criteria. Lifestyle interventions improved lipid levels in 10 of 18 studies and blood pressure in 4 of 9 studies. Most guidelines recommended hypertension screening at least every 2 years and dyslipidemia screening every 5 years, but recommendations for who should receive dyslipidemia screening varied. One study indicated that 82% of women of reproductive age received hypertension screening during the preceding year. In another study, only 49% of women aged 20 to 45 years received recommended dyslipidemia screening. Conclusions Lifestyle interventions may offer modest benefits for reducing blood pressure and lipids in this population. Inconsistency among recommendations for dyslipidemia screening may contribute to low screening rates. Future studies should clarify predictors of and barriers to cholesterol screening in this population.


Introduction
Cardiovascular disease (CVD) is the leading cause of death in women (1) and the third leading cause of death among women of reproductive age (defined as 18-44 y unless otherwise specified) (2). The prevalence of hypertension and dyslipidemia, 2 major CVD risk factors, is relatively high among women of reproductive age. During 2005 through 2008, 8% of women aged 20 to 44 years had hypertension or were taking hypertension medication (2), and 11% had dyslipidemia (2). Although hypertension prevalence rates have remained stable during the last 10 years, approximately 40% of reproductive-aged adults (both men Centers for Disease Control and Prevention • www.cdc.gov/pcd/issues/2011/nov/11_0029.htm The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. and women) with hypertension are unaware they have the condition (3).
Overall, women of reproductive age are not generally considered to be at high risk for CVD, but identification of hypertension and dyslipidemia has reproductive health significance. For women of reproductive age with hypertension, combined hormonal contraceptive methods are generally not recommended because they may increase CVD risk. Additionally, hypertension during pregnancy is associated with adverse outcomes such as preeclampsia, placenta abruption, preterm delivery, low birth weight, and infant death (4)(5)(6)(7). Dyslipidemia is associated with polycystic ovary syndrome (8), the most common endocrine disorder among women of reproductive age and a leading cause of infertility (9). Dyslipidemia during pregnancy may also have adverse effects on both the fetus and mother (10,11).
Because women of reproductive age are at risk of becoming pregnant and drug therapy may pose risks to the fetus, lifestyle modifications are often the first line of treatment for hypertension or dyslipidemia. The effectiveness of lifestyle interventions such as exercise and diet on cardiovascular outcomes is well established for men and older women (12)(13)(14)(15)(16)(17)(18), but their effects on women of reproductive age are largely unknown. Reviewing hypertension and dyslipidemia screening recommendations for consistency between guidelines and understanding screening prevalence for women of reproductive age may clarify intervention referral opportunities. To our knowledge, no published reports have compared screening guidelines as they pertain to this population.
The primary objective of this systematic review was to evaluate the evidence from randomized controlled trials (RCTs) that have investigated the effects of lifestyle interventions on hypertension, dyslipidemia, or CVD illness and death in this population. Secondary objectives were to review hypertension and dyslipidemia recommendations for consistency and to report the prevalence of screening among women of reproductive age.

Data sources
Using electronic bibliographic databases (PubMed/ MEDLINE, Cochrane Database of Systematic Reviews, and US National Guideline Clearinghouse), we conducted electronic searches on lifestyle interventions, national hypertension and dyslipidemia screening guidelines, and screening prevalence for women of reproductive age from January 1, 1990, through November 18, 2010. We also searched for relevant guidelines published by the American College of Obstetricians and Gynecologists. To conduct the search, we used a combination of free text terms and concepts derived from the National Library of Medicine's medical subject headings (Table 1). We applied additional filter options (English language and human studies) and related search features in iterative fashion to identify all relevant literature. In addition, we reviewed reference lists from retrieved articles and searched the grey literature, which consists of reports, studies, articles, and monographs produced by federal and local government agencies, private organizations, and educational institutions.

Lifestyle interventions
Two researchers (S.T., M.T.) searched the literature independently and selected studies on the basis of a priori inclusion criteria. We used researcher agreement to reconcile questions that arose about eligibility. We found no systematic reviews or meta-analyses of the effect of lifestyle interventions on CVD illness or death that focused on women of reproductive age or that parsed data to allow such analysis. Therefore, we used the following a priori inclusion criteria to identify individual studies: 1) RCTs or randomized crossover study designs; 2) enrolled 10 or more women of reproductive age or whose sample included subgroup analyses for women of reproductive age, or both; 3) full-length article; 4) outcomes of blood pressure, lipids, or CVD illness or death, or all; 5) diet or exercise intervention or both; and 6) published in the English language. Twentyone of 555 studies (3.8%) met all a priori selection criteria and addressed 1 or more relevant outcomes (Figure).

Screening recommendations
Of particular interest to this review was an examination of guidelines likely to be in current use. As such, we focused on national-level US-based guidelines. We examined evidence-based guidelines produced under the auspices of medical specialty associations, relevant professional societies, and federal government agencies that had been reviewed, revised, or developed within the last , which continue to be referenced by other current guidelines. To be included in our assessment, a guideline had to meet the evidencebased criteria required for acceptance in the National Guideline Clearinghouse (www.guideline.gov/about/inclusion-criteria.aspx).

Screening prevalence
To describe current hypertension and dyslipidemia screening practices in the target population, we focused our searches on studies emanating from large population-based surveys in the United States, including the Behavioral Risk Factors Surveillance System (BRFSS), the Medical Expenditure Panel Survey (MEPS), the National Ambulatory Medical Care Survey (NAMCS), the National Health Interview Survey (NHIS), the National Health and Nutrition Examination Survey (NHANES), and the National Survey of Family Growth (NSFG).

Data extraction
We extracted data from included studies into comprehensive evidence tables to facilitate assessment of the quality of the individual studies. For the purposes of this report, we present details on the study setting and population, intervention, results (significant changes in outcomes in intervention groups relative to controls), and study quality from lifestyle intervention articles. We present included studies in descending chronological order, identified by first author and year (Tables 2, 3, and 4). We used a validated instrument designed to evaluate the internal validity of controlled studies to assess the quality of each of the studies. ECRI Institute (Plymouth Meeting, Pennsylvania) developed the instrument, which is available on request from the authors (19). We made no attempt to analyze or synthesize the findings quantitatively because of the large variation in the interventions assessed. Instead, we summarize the data qualitatively.
We extracted the following elements from hypertension and dyslipidemia guidelines: year, target population, recommended screening interval for all healthy and at-risk women of reproductive age, risk factors, and diagnostic criteria (Table 5). Lastly, we describe screening prevalence estimates for hypertension and dyslipidemia among women of reproductive age obtained from 2 studies that used population-based surveys.

Lifestyle interventions
Of 555 retrieved references, we identified 21 studies that met our inclusion criteria, including diet interventions (n = 3), exercise interventions (n = 13), and combined diet and exercise interventions (n = 5). Eighteen studies examined the effect of an intervention on lipid levels, 9 examined blood pressure measures, and none focused on CVD illness or death. Study follow-up ranged from 6 weeks to 2 years. After reading the abstracts or the entire text, we excluded approximately 96% of the studies (534 of 555) largely because data precluded separate analyses of women of reproductive age (78%) (Figure). Additionally, 14% were excluded because our targeted outcomes were not addressed, and 8% were not RCTs or crossover study designs. We summarized findings from the trials that investigated the effect of diet, exercise, and combined diet and exercise interventions on systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG).

Diet alone
We summarized data from 3 low-to moderate-quality, randomized crossover studies (20-22) involving 86 women of reproductive age that met our inclusion criteria ( Table  2). All examined lipid levels and 1 also examined blood pressure measures (21). Study settings included Australia and the United States, and all studies compared low-fat to higher-fat diets and reported reduced mean values in TC (10.8-30.2 mg/dL), LDL-C (8.7-26.3 mg/dL), and HDL-C (3.4-10.1 mg/dL) for participants who followed lowfat diets. The study that examined blood pressure reported significant mean reductions in DBP (4.4 mm Hg) and arterial pressure (3.8 mm Hg) but not SBP for participants following a low-fat diet.

Exercise alone
Thirteen RCTs (12 moderate quality, 1 high quality) involved 482 women of reproductive age (

Combined diet and exercise interventions
Five RCTs (1 low quality, 3 moderate quality, 1 high quality) representing 443 women of reproductive age (Table 4) examined TC, HDL-C, and TG; 3 examined LDL-C (36-38); and 3 examined blood pressure (38-40). Interventions varied in duration, ranging from 14 weeks to 2 years. Study settings were Canada, Finland, Italy, and the United States. The high-quality RCT was the most recent study, had the largest sample (120 obese women of reproductive age), the longest intervention period, and provided monthly sessions with a nutritionist and exercise trainer for the first year and bimonthly sessions in the second year (39). Interventions tested in the other RCTs included weight-reduction diets coupled with walking and group education (40) or with aerobics or resistance training (36); and aerobic exercise with low-fat diet and group education (38) or with fish diet (37).
Only 1 US RCT (38) found significant protective differences among the intervention groups relative to controls for TC and LDL-C reporting mean decreases in TC for the diet plus exercise group (10.8 mg/dL) and diet only (15.1 mg/dL), and in LDL-C for both intervention groups (11.2 and 10.9 mg/dL, respectively). One RCT focusing on obese women reported a 8.0 mg/dL mean increase in HDL-C among the intervention group (39). Four RCTs showed no effect of diet and exercise on HDL-C (36-38,40).

Current recommendations for hypertension and dyslipidemia screening and lifestyle modifications
Seven national US guidelines containing recommendations for hypertension and dyslipidemia screening were The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
identified ( Table 5). The guidelines for hypertension screening intervals and diagnostic criteria among women of reproductive age were generally consistent. Less agreement was observed between guidelines in the criteria for diagnosing dyslipidemia and cholesterol screening recommendations for women of reproductive age.
Five of the guidelines explicitly or by deferral to the NHLBI JNC7 guidelines (41) recommend hypertension screening every 2 years for adult women with optimal blood pressure (<120/80 mm Hg) and more frequently for those who have prehypertension or have other risk factors (41-46) ( Table 5). Guidelines differ with regard to age at which hypertension screening should begin. The guidelines also vary in definitions of at-risk populations, but the following risk factors are consistent across guidelines: smoking, diabetes, obesity, physical inactivity, older age (>65 years for women), and having a personal or family history of premature CVD, hypertension, or dyslipidemia (<65 y for women and <55 y for men). The American Heart Association (AHA) also addresses pregnancy conditions and other gender-related comorbidities that identify women at risk (43). All organizations recommend that a series of standardized blood pressure measurements be taken over multiple visits before a diagnosis of hypertension is made, but there are nuanced differences between guidelines.
Lifestyle modifications, in particular exercise and weight reduction, were universally recommended by all guidelines as an integral part of CVD prevention and as first-line treatment for milder forms of hypertension. In addition, most recommend smoking cessation, maintaining a healthy diet rich in fruits and vegetables, and reducing alcohol and sodium intake.
National cholesterol guidelines concur that women at increased risk of coronary heart disease (CHD) should be screened for dyslipidemia. However, only AHA (43) and NHLBI Adult Treatment Program III (48) recommend screening women of reproductive age (≥20 y) who are not at increased risk. Increased risk is generally defined by the presence of 1 or more of the following: diabetes, previous personal history of CHD or noncoronary atherosclerosis, a family history of premature CVD, current tobacco use, hypertension, or obesity. Screening frequency recommendations are similar, generally every 5 years, with shorter intervals for women whose lipid levels are close to warranting therapy, and longer intervals for those not at increased risk if they have repeatedly had normal lipid levels. Most organizations recommend that a full lipid profile be obtained and that lipid screening be performed after a fast of 9 to 12 hours. However, there is some disagreement between guidelines about the need for fasting blood levels and the value of including triglycerides as a part of the initial tests (49). Furthermore, consensus about diagnostic criteria for dyslipidemia is lacking (Table  5). Most guidelines recommend the same CVD risk reduction lifestyle modifications for cholesterol management as mentioned previously for hypertension, except sodium reduction. Additionally, they emphasize high-fiber, low-fat diets.

Screening prevalence
We identified only 2 hypertension and dyslipidemia screening prevalence studies that used population-based data and included women of reproductive age. The sole report that examined hypertension screening rates among women of reproductive age (defined as 14-44 y) was based on 1988 NSFG data (50) and estimated annual hypertension screening within the preceding year to be 82.3%. Predictors of hypertension screening among women of reproductive age in that report included having had a family planning visit in the previous 12 months, current or recent pregnancy, history of hypertension, older age, black race, and higher education or income (50). Only 1 study reported cholesterol screening rates among women of reproductive age, and it used 1999-2006 National Health and Nutrition Examination Survey (NHANES) data (51).
That study reported 49% of women aged 20 to 45 years with no CHD risk factors received cholesterol screening within the preceding 5 years. Screening rates were 52% among women with 1 risk factor and 69% among those with CHD or CHD equivalent risk.

Discussion
Limited conclusions can be drawn about lifestyle interventions in women of reproductive age because of the small number of included RCTs, the heterogeneity of interventions examined, and the lack of consistent findings across studies. Lifestyle interventions improved dyslipidemia in 10 of 18 studies and hypertension in 4 of 9 studies. Stronger benefit was seen on levels of TC and LDL-C than on HDL-C or TG. Improvements in systolic blood pressure were seen in 3 of 9 studies that examined blood pressure changes. Diastolic blood pressure improved in 4 of 9 studies. Follow-up tended to be short-term (1-2 y), and most samples comprised healthy women of reproductive age. Centers for Disease Control and Prevention • www.cdc.gov/pcd/issues/2011/nov/11_0029.htm The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Our assessment of the effectiveness of lifestyle intervention is consistent with reviews conducted on low-risk populations. A systematic review of lifestyle interventions among healthy adult men and women also concluded that lifestyle interventions offered marginal short-term benefit on blood pressure and, to a lesser degree, lipids (52). Two meta-analyses examined the effect of aerobic exercise on blood pressure and found modest reductions among normotensive, mostly older women (13,53). The effects of lifestyle interventions on lipids appear to be strongest for LDL-C and TC and weaker for any benefit to HDL-C or TG, consistent with similar investigations (14,54). Previous reports indicated mixed findings regarding the effect of exercise on TG and HDL-C levels; improvements were reported for physically inactive subjects primarily. Indeed, that was the case for the studies in which we found improvements in TG and HDL-C (38,39). Finally, exercise duration may be the most important predictor of change to HDL-C (55,56); the 2 studies reporting improvements in TG and HDL-C levels had the longest intervention duration (1-2 y).
The review of guidelines revealed that diagnostic criteria and screening recommendations for dyslipidemia vary. Optimal screening tests include measurement of total and HDL-C levels or apolipoproteins without fasting and without regard to triglycerides (49). Updated NHLBI guidelines for hypertension and dyslipidemia screening are anticipated in 2012.
We found only 1 study that examined prevalence of hypertension screening and another for dyslipidemia screening among women of reproductive age. One study reported 82% of women of reproductive age received hypertension screening within the preceding year (50), which is higher than a current estimate of 75% screened (according to unpublished National Health Interview Survey [NHIS] data analyses, women aged 14-44 y, 2008). However, nearly 90% of women of reproductive age get hypertension screening within the recommended interval of every 2 years (NHIS data analyses, 2008). Kuklina et al also reported that 49% to 69% of women aged 20 to 45 years had their cholesterol checked in the previous 5 years (51), which is consistent with estimates from 2008 NHIS unpublished analyses for the same population (64%). The lack of consensus among dyslipidemia screening guidelines may be the reason for lower screening rates in this population.
Few studies provide detailed examination of hypertension and dyslipidemia screening prevalence among women of reproductive age. Perhaps this gap in the literature exists because young people tend to be healthy and the age gradient is marked in these conditions, so women of reproductive age have not been considered a target for screening surveillance. However, identification of high-risk subpopulations and clarification of screening recommendations may prevent the onset of hypertension, dyslipidemia, and other chronic conditions such as diabetes among those at increased risk for CVD.
Substantial body of evidence establishes that diet and exercise improve hypertension and dyslipidemia, but that literature is predominantly based on studies of men and older women. Individual study samples included in this review may lack the power to detect the benefits of lifestyle interventions among healthy populations. For example, pooled results among RCTs that enrolled healthy older women detected significant effects between aerobic exercise and blood pressure, although the individual RCT findings were not significant (53). Pooling studies in metaanalyses can add the needed statistical power to detect modest short-term benefits of lifestyle interventions, but not enough studies are focused on women of reproductive age to do this.
Women of reproductive age are a population in need of CVD screening and early intervention. Lifestyle modifications are appropriate initial therapies for most patients and may reduce CVD risk through mechanisms other than lowering LDL-C or blood pressure, such as through smoking cessation, weight reduction, and increased physical activity (48). Moreover, a dose-response effect of physical activity on CHD risk suggests that higher intensity exercise conveys greater benefit (57-59).      Intervention. Twelve wks weight reduction diet followed by maintenance program for 0 wks with weekly small group meetings and random assignment to walk-1 (n = 2), walk-2 (n = 23), or control (n = 2);